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1.
Sci Rep ; 12(1): 11729, 2022 07 11.
Article in English | MEDLINE | ID: mdl-35821511

ABSTRACT

Highly pathogenic avian influenza (HPAI) viruses of the A/Goose/Guangdong/1/1996 lineage (GsGd), which threaten the health of poultry, wildlife and humans, are spreading across Asia, Europe, Africa and North America but are currently absent from South America and Oceania. In December 2021, H5N1 HPAI viruses were detected in poultry and a free-living gull in St. John's, Newfoundland and Labrador, Canada. Our phylogenetic analysis showed that these viruses were most closely related to HPAI GsGd viruses circulating in northwestern Europe in spring 2021. Our analysis of wild bird migration suggested that these viruses may have been carried across the Atlantic via Iceland, Greenland/Arctic or pelagic routes. The here documented incursion of HPAI GsGd viruses into North America raises concern for further virus spread across the Americas by wild bird migration.


Subject(s)
Influenza A Virus, H5N1 Subtype , Influenza A virus , Influenza in Birds , Animals , Animals, Wild , Europe/epidemiology , Geese , Humans , Influenza A Virus, H5N1 Subtype/genetics , Influenza in Birds/epidemiology , North America/epidemiology , Phylogeny , Poultry
2.
Int J Pharm ; 622: 121829, 2022 Jun 25.
Article in English | MEDLINE | ID: mdl-35580686

ABSTRACT

The oral route is the best way to administer a drug; however, fitting peptide drugs in this route is a major challenge. In insulin cases, less than 0.5% of the administered dose achieves systemic circulation. Oral delivery by nanoparticles can increase insulin permeability across the intestinal epithelium while maintaining its structure and activity until release in the gut. This system can be improved to increase permeability across intestinal cells through active delivery. This study aimed to improve a nanoparticle formulation by promoting functionalization of its surface with immunoglobulin G to increase its absorption by intestinal epithelium. The characterization of formulations showed an adequate size and a good entrapment efficiency. Functionalized nanoparticles led to a desirable increase in insulin release time. Differential scanning calorimetry, infrared spectroscopy and paper chromatography proved the interactions of nanoparticle components. With immunoglobulin G, the nanoparticle size was slightly increased, which did not show aggregate formation. The developed functionalized nanoparticle formulation proved to be adequate to carry insulin and potentially increase its internalization by epithelial gut cells, being a promising alternative to the existing formulations for orally administered low-absorption peptides.


Subject(s)
Insulin , Nanoparticles , Administration, Oral , Drug Carriers/chemistry , Immunoglobulin G , Nanoparticles/chemistry , Pharmaceutical Preparations , Polymers/chemistry
3.
Pharm Dev Technol ; 25(9): 1053-1062, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32558594

ABSTRACT

The aim of this study was to propose the use of spray-dried mucoadhesive carvedilol-loaded nanocapsules in the formulation of sublingual tablets. There is no previous report describing the preparation of tablets containing spray-dried nanocapsules or tablets containing nanocapsules, neither prepared by direct compression nor for sublingual administration. Tablets of 6 mm of diameter and 2.7 ± 0.2 mm of height were obtained with a mean weight of 44 ± 4 mg, carvedilol content of 0.164 ± 0.017 mg, and a disintegration time less than 25 min. They were produced using a force of 4.7 ± 1.6 kgf. The release profile of carvedilol from the tablets was evaluated using the dialysis bag method. In parallel, the release of nanocapsules from the tablet structure into the release medium was evaluated using dynamic light scattering. Nanocapsules that were released from the tablets into the release medium exhibited similar particle size distributions after recovery as in their original liquid suspension, without losing their original ability to control drug release. Therefore, sublingual tablets may be produced from spray-dried drug-loaded nanocapsules using a direct compression technique, providing a useful pharmaceutical approach for drugs that undergo first pass metabolism, such as carvedilol.


Subject(s)
Carvedilol/chemistry , Nanocapsules/chemistry , Tablets/chemistry , Administration, Sublingual , Chemistry, Pharmaceutical/methods , Drug Liberation/drug effects , Nanomedicine/methods , Particle Size , Polymers/chemistry , Suspensions/chemistry
4.
Drug Deliv Transl Res ; 10(6): 1829-1840, 2020 12.
Article in English | MEDLINE | ID: mdl-32562254

ABSTRACT

We developed a pectin-based hydrogel containing nanocapsules as a new strategy for melanoma treatment. Our first objective was to evaluate the nanoencapsulation effect of imiquimod on melanoma. Imiquimod-loaded polymeric nanocapsules (NCimiq) showed significant time-dependent decrease in cell viability after treatment at 3 µmol L-1 (79% viable cells in 24 h and 55% in 72 h), which was not observed in cells treated with the solution of the drug (IMIQ) (99% viable cells in 24 h and 91% in 72 h). The second objective was to develop the hydrogel containing the drug-loaded nanocapsules (PEC-NCimiq). In vitro release study showed that 63% of imiquimod was released from the pectin-based hydrogel containing the drug (PEC-imiq) after 2 h, while 60% of the drug was released from PEC-NCimiq after 8 h. In the permeation study, 2.5 µg of imiquimod permeated the skin within 8 h after the initial contact of PEC-NCimiq, whereas only 2.1 µg of drug permeated after 12 h of contact when PEC-imiq was assayed. Pectin-based hydrogels enabled the drug penetration in all skin layers, especially the dermis (PEC-NCimiq = 6.8 µg and PEC-imiq = 4.3 µg). In the adhesion study, PEC-NCimiq showed the highest adhesiveness (42% removed from the skin) in comparison to PEC-imiq (71% removed from the skin). In conclusion, the nanoencapsulation provided a higher cytotoxic effect of imiquimod in SK-MEL-28, and the incorporation of the drug-loaded nanocapsules in pectin-based hydrogel showed higher adhesiveness and deeper penetration of the drug into the skin. Graphical abstract.


Subject(s)
Hydrogels , Imiquimod/administration & dosage , Melanoma , Nanocapsules , Pectins , Animals , Cell Line, Tumor , Humans , Melanoma/drug therapy , Swine
5.
AAPS PharmSciTech ; 21(2): 54, 2020 Jan 06.
Article in English | MEDLINE | ID: mdl-31907712

ABSTRACT

Cervical cancer is associated with the human papilloma virus (HPV) and nowadays is the fourth most frequent cancer among women. One of the treatments for this disease is based on the application of imiquimod. In this study, we postulated that the use of imiquimod in nanoemulsion results in a better antitumoral effect than the drug administered in its nonencapsulated form for the treatment of cervical cancer. Permeability studies using vaginal mucosa, as membrane, and in vitro studies involving cervical cancer cells (viability, clonogenic assay, and cell death analysis) were performed. We showed that low amount of encapsulated imiquimod permeated the vaginal mucosa. However, a higher percentage of cells died after the treatment with low amount (3.0 µmol L-1) of the formulation compared to the free drug. In addition, the innovative formulation presented a combinatory mechanism of cell death involving autophagy and apoptosis. Our results demonstrate that the imiquimod-loaded nanoemulsioncan be an alternative product for the treatment of cervical cancer validating the hypothesis.


Subject(s)
Imiquimod/administration & dosage , Papillomaviridae/drug effects , Uterine Cervical Neoplasms/drug therapy , Animals , Cell Line, Tumor , Drug Compounding , Emulsions , Female , Humans , Nanoparticles , Swine , Uterine Cervical Neoplasms/virology
6.
Eur J Pharm Biopharm ; 136: 9-17, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30630060

ABSTRACT

This paper proposes the development of imiquimod-loaded polymeric nanocapsules formulation for the treatment of cervical cancer. The mechanism of death involved in the reduction of the cell viability as well as the production of an inflammation marker (IL-6) after the treatment in cell line SiHa have been evaluated. The formulation has significantly decreased the viability of the cells in a time-dependent manner, after 24, 48 and 72 h. Additionally, results showed a cellular decrease of almost 80% of the cells after 72 h of treatment. The formulation induced death by apoptosis, necrosis, autophagy, and increased the percentage of SubG1subpopulation of SiHa cells after 72 h. After the same time-interval, the formulation significantly prevented the appearance of colonies, showing effectiveness against SiHa. Finally, the formulation stimulated SiHa cells to release IL-6. These findings open new possibilities for the development of aqueous nanosuspension containing imiquimod as a novel strategy for the treatment of cervical cancer.


Subject(s)
Antineoplastic Agents/administration & dosage , Cytotoxins/administration & dosage , Drug Carriers/administration & dosage , Imiquimod/administration & dosage , Nanocapsules/administration & dosage , Uterine Cervical Neoplasms , Antineoplastic Agents/metabolism , Apoptosis/drug effects , Apoptosis/physiology , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/physiology , Cytotoxins/metabolism , Drug Carriers/metabolism , Female , Humans , Imiquimod/metabolism , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/metabolism
7.
Biomed Pharmacother ; 94: 10-20, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28750355

ABSTRACT

Doxazosin has been evaluated for the treatment of several types of cancer. Here, the antitumor effect of the nanoencapsulated form of doxazosin was evaluated in an in vitro model of breast cancer (MCF7 cell line). Doxazosin-loaded polymeric nanocapsules (DXZ-NC) were produced by interfacial deposition of preformed polymer with homogeneous aspect, spherical shape, mean diameter of about 130nm, positive zeta potential (+5mV), and encapsulation efficiency close to 35%. The Alamar Blue® assay and cell counting were carried out to assess cell viability and cell number, respectively. Mechanism of death was evaluated by Annexin/Propidium Iodide staining, while the long-term response was assessed using the clonogenic assay. Nuclear morphometric analysis was investigated using the NMA technique. A significant decrease in cell viability and clonogenicity was observed after the treatment with DXZ-NC when compared to the non-encapsulated drug. All treatments induced apoptosis as the main mechanism of toxicity. In conclusion, the nanoencapsulation of doxazosin improved its in vitro effects in MCF7 cells, without changing the mechanism of cell death underlying its toxicity. This approach was fundamental to reduce the long-term in vitro ability of the remaining tumor cells to form new colonies after the treatment, potentially reducing the risk of tumor recurrence.


Subject(s)
Breast Neoplasms/pathology , Doxazosin/pharmacology , Nanocapsules/chemistry , Cell Count , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Cell Proliferation/drug effects , Cell Survival/drug effects , Clone Cells , Drug Liberation , Female , Humans , MCF-7 Cells , Nanocapsules/ultrastructure , Particle Size
8.
Parasitology ; 144(13): 1769-1774, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28653597

ABSTRACT

New oral treatments are needed for all forms of leishmaniasis. Here, the improved oral efficacy of quercetin (Qc) and its penta-acetylated derivative (PQc) was evaluated in cutaneous leishmaniasis after encapsulation in lipid-core nanocapsules (LNCs) of poly(ε-caprolactone). Leishmania amazonensis-infected BALB/c mice were given 51 daily oral doses of free drugs (16 mg kg-1) or LNC-loaded drugs (0·4 mg kg-1). While treatment with free Qc reduced the lesion sizes and parasite loads by 38 and 71%, respectively, LNC-Qc produced 64 and 91% reduction, respectively. The antileishmanial efficacy of PQc was similar but not as potently improved by encapsulation as Qc. None of the treatments increased aspartate aminotransferase, alanine aminotransferase or creatinine serum levels. These findings indicate that when encapsulated in LNC, Qc and, to a lesser extent, PQc can safely produce an enhanced antileishmanial effect even at a 40-fold lower dose, with implications for the development of a new oral drug for cutaneous leishmaniasis.


Subject(s)
Leishmania mexicana/drug effects , Nanocapsules , Polyesters/analysis , Quercetin/pharmacology , Trypanocidal Agents/pharmacology , Animals , Female , Leishmaniasis, Cutaneous/drug therapy , Lipids/analysis , Mice , Mice, Inbred BALB C
9.
Transbound Emerg Dis ; 64(5): e22-e26, 2017 Oct.
Article in English | MEDLINE | ID: mdl-27297961

ABSTRACT

Recently, a novel atypical porcine pestivirus (APPV) with significant distribution was described in the USA. Subsequent screening of the German pig sector showed a high prevalence of APPV with high variability among strains. First indication of a cell culture isolate is provided which will allow further investigations like pathogenesis studies.


Subject(s)
Genetic Variation , Pestivirus Infections/veterinary , Pestivirus/genetics , Swine Diseases/epidemiology , Animals , Germany/epidemiology , Pestivirus/isolation & purification , Pestivirus Infections/epidemiology , Pestivirus Infections/virology , Phylogeny , Prevalence , Sequence Analysis, DNA/veterinary , Swine , Swine Diseases/virology
10.
Transbound Emerg Dis ; 64(6): 1813-1824, 2017 Dec.
Article in English | MEDLINE | ID: mdl-27860371

ABSTRACT

Outbreaks of highly pathogenic avian influenza A virus (HPAIV) subtype H5N8, clade 2.3.4.4, were first reported in January 2014 from South Korea. These viruses spread rapidly to Europe and the North American continent during autumn 2014 and caused, in Germany, five outbreaks in poultry holdings until February 2015. In addition, birds kept in a zoo in north-eastern Germany were affected. Only a few individual white storks (Ciconia ciconia) showed clinical symptoms and eventually died in the course of the infection, although subsequent in-depth diagnostic investigations showed that other birds kept in the same compound of the white storks were acutely positive for or had undergone asymptomatic infection with HPAIV H5N8. An exception from culling all of the 500 remaining zoo birds was granted by the competent authority. Restriction measures included grouping the zoo birds into eight epidemiological units in which 60 birds of each unit tested repeatedly negative for H5N8. Epidemiological and phylogenetical investigations revealed that the most likely source of introduction was direct or indirect contact with infected wild birds as the white storks had access to a small pond frequented by wild mallards and other aquatic wild birds during a period of 10 days in December 2014. Median network analysis showed that the zoo bird viruses segregated into a distinct cluster of clade 2.3.4.4 with closest ties to H5N8 isolates obtained from mute swans (Cygnus olor) in Sweden in April 2015. This case demonstrates that alternatives to culling exist to rescue valuable avifaunistic collections after incursions of HPAIV.


Subject(s)
Disease Outbreaks/veterinary , Influenza A Virus, H5N8 Subtype/isolation & purification , Influenza in Birds/epidemiology , Animal Culling , Animals , Animals, Zoo , Birds , Germany/epidemiology , High-Throughput Nucleotide Sequencing/veterinary , Influenza A Virus, H5N8 Subtype/genetics , Influenza A Virus, H5N8 Subtype/immunology , Influenza A Virus, H5N8 Subtype/pathogenicity , Influenza in Birds/pathology , Influenza in Birds/virology , Phylogeny , Sequence Analysis, DNA/veterinary
11.
J Nanosci Nanotechnol ; 16(2): 1310-20, 2016 Feb.
Article in English | MEDLINE | ID: mdl-27433581

ABSTRACT

An innovative nanocapsule formulation for parenteral administration using selected vegetable oils (mango, jojoba, pequi, oat, annatto, calendula, and chamomile) was developed that has the potential to encapsulate various drugs. The vegetable oil-loaded nanocapsules were prepared by interfacial deposition and compared with capric/caprylic triglyceride-loaded lipid core nanocapsules. The major objective was to investigate the effect of vegetable oils on particle size distribution and physical stability and to determine the hemolytic potential of the nanocapsules, considering their applicability for intravenous administration. Taking into account the importance of accurately determining particle size for the selected route of administration, different size characterization techniques were employed, such as Laser Diffraction, Dynamic Light Scattering, Multiple Light Scattering, Nanoparticle Tracking Analysis, and Transmission Electronic Microscopy. Laser diffraction studies indicated that the mean particle size of all nanocapsules was below 300 nm. For smaller particles, the laser diffraction and multiple light scattering data were in agreement (D[3,2]-130 nm). Dynamic light scattering and nanoparticle tracking analysis, two powerful techniques that complement each other, exhibited size values between 180 and 259 nm for all nanoparticles. Stability studies demonstrated a tendency of particle creaming for jojoba-nanocapsules and sedimentation for the other nanoparticles; however, no size variation occurred over 30 days. The hemolysis test proved the hemocompatibility of all nanosystems, irrespective of the type of oil. Although all developed nanocapsules presented the potential for parenteral administration, jojoba oil-loaded nanocapsules were selected as the most promising nanoformulation due to their low average size and high particle size homogeneity.


Subject(s)
Nanocapsules/chemistry , Plant Oils , Female , Humans , Infusions, Parenteral , Male , Particle Size , Plant Oils/chemistry , Plant Oils/pharmacokinetics , Plant Oils/pharmacology
12.
Int J Pharm ; 507(1-2): 12-20, 2016 Jun 30.
Article in English | MEDLINE | ID: mdl-27130364

ABSTRACT

For an improved understanding of the relevant particle features for cutaneous use, we studied the effect of the surface charge of acrylic nanocapsules (around 150nm) and the effect of a chitosan gel vehicle on the particle penetration into normal and stripped human skin ex vivo as well as local tolerability (cytotoxicity and irritancy). Rhodamin-tagged nanocapsules penetrated and remained in the stratum corneum. Penetration of cationic nanocapsules exceeded the penetration of anionic nanocapsules. When applied on stripped skin, however, the fluorescence was also recorded in the viable epidermis and dermis. Cationic surface charge and embedding the particles into chitosan gel favored access to deeper skin. Keratinocytes took up the nanocapsules rapidly. Cytotoxicity (viability<80%), following exposure for ≥24h, appears to be due to the surfactant polysorbate 80, used for nanocapsules stabilization. Uptake by fibroblasts was low and no cytotoxicity was observed. No irritant reactions were detected in the HET-CAM test. In conclusion, the surface charge and chitosan vehicle, as well as the skin barrier integrity, influence the skin penetration of acrylic nanocapsules. Particle localization in the intact stratum corneum of normal skin and good tolerability make the nanocapsules candidates for topical use on the skin, provided that the polymer wall allows the release of the active encapsulated substance.


Subject(s)
Chitosan/administration & dosage , Chitosan/chemistry , Nanocapsules/administration & dosage , Nanocapsules/chemistry , Skin Absorption/drug effects , Cell Survival/drug effects , Cells, Cultured , Chitosan/adverse effects , Chitosan/pharmacokinetics , Dermis/metabolism , Epidermis/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Gels/administration & dosage , Gels/adverse effects , Gels/chemistry , Humans , Keratinocytes/drug effects , Keratinocytes/metabolism , Nanocapsules/adverse effects , Particle Size , Polymethacrylic Acids/administration & dosage , Polymethacrylic Acids/adverse effects , Polymethacrylic Acids/chemistry , Polysorbates/administration & dosage , Polysorbates/adverse effects , Polysorbates/chemistry , Surface Properties
13.
J Control Release ; 223: 207-214, 2016 Feb 10.
Article in English | MEDLINE | ID: mdl-26686081

ABSTRACT

The treatment of various hair disorders has become a central focus of good dermatologic patient care as it affects men and women all over the world. For many inflammatory-based scalp diseases, glucocorticoids are an essential part of treatment, even though they are known to cause systemic as well as local adverse effects when applied topically. Therefore, efficient targeting and avoidance of these side effects are of utmost importance. Optimizing the balance between drug release, interfollicular permeation, and follicular uptake may allow minimizing these adverse events and simultaneously improve drug delivery, given that one succeeds in targeting a sustained release formulation to the hair follicle. To test this hypothesis, three types of polymeric nanocarriers (nanospheres, nanocapsules, lipid-core nanocapsules) for the potent glucocorticoid clobetasol propionate (CP) were prepared. They all exhibited a sustained release of drug, as was desired. The particles were formulated as a dispersion and hydrogel and (partially) labeled with Rhodamin B for quantification purposes. Follicular uptake was investigated using the Differential Stripping method and was found highest for nanocapsules in dispersion after application of massage. Moreover, the active ingredient (CP) as well as the nanocarrier (Rhodamin B labeled polymer) recovered in the hair follicle were measured simultaneously, revealing an equivalent uptake of both. In contrast, only negligible amounts of CP could be detected in the hair follicle when applied as free drug in solution or hydrogel, regardless of any massage. Skin permeation experiments using heat-separated human epidermis mounted in Franz Diffusion cells revealed equivalent reduced transdermal permeability for all nanocarriers in comparison to application of the free drug. Combining these results, nanocapsules formulated as an aqueous dispersion and applied by massage appeare to be a good candidate to maximize follicular targeting and minimize drug penetration into the interfollicular epidermis. We conclude that such nanotechnology-based formulations provide a viable strategy for more efficient drug delivery to the hair follicle. Moreover, they present a way to minimize adverse effects of potent glucocorticoids by releasing the drug in a controlled manner and simultaneously decreasing interfollicular permeation, offering an advantage over conventional formulations for inflammatory-based skin/scalp diseases.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Clobetasol/administration & dosage , Hair Follicle/metabolism , Nanocapsules/administration & dosage , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacokinetics , Clobetasol/chemistry , Clobetasol/pharmacokinetics , Drug Liberation , Humans , Hydrogels , Physical Stimulation , Polyesters/chemistry , Swine
14.
Klin Monbl Augenheilkd ; 232(12): 1386-91, 2015 Dec.
Article in German | MEDLINE | ID: mdl-26678901

ABSTRACT

The value of diffusion-weighted magnet resonance imaging (DWI-MRI) has been demonstrated for an ever growing range of clinical indications. DWI is sensitive to the diffusion of water molecules and probes their random displacement within tissue. DWI provides both qualitative and quantitative information on tissue characteristics, e.g. tissue cellularity. This review provides an overview of diffusion-weighted imaging and its emerging applications in ophthalmology. The basic physics and technical foundations of DWI are introduced. The emerging applications of DWI are surveyed, particularly in diseases of the eye, orbit and optical nerve.


Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Eye Diseases/pathology , Image Enhancement/methods , Orbital Diseases/pathology , Humans
15.
Pharmazie ; 70(3): 155-64, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25980176

ABSTRACT

The aim of this work was to develop solid lipid nanoparticles (SLN) containing copaiba oil with and without allantoin (NCOA, NCO, respectively) and to evaluate their antifungal activity. Nanoparticle suspensions were prepared using a high homogenisation technique and characterised by dynamic light scattering, laser diffraction, nanoparticle tracking analysis, multiple light scattering analysis, high-pressure liquid chromatography, pH and rheology. The antifungal activities of the formulations were tested in vitro against the emergent yeasts Candida krusei and Candida parapsilosis, and the fungal pathogens of human skin Trichophyton rubrum and Microsporum canis. The dynamic light scattering analysis showed z-average diameters (intensity) between 118.63 ± 8.89 nm for the nanoparticles with both copaiba oil and allantoin and 126.06 ± 9.84nm for the nanoparticles with just copaiba oil. The D[4,3] determined by laser diffraction showed similar results of 123 ± 1.73 nm for the nanoparticles with copaiba oil and allantoin and 130 ± 3.6 nm for the nanoparticles with copaiba oil alone. Nanoparticle tracking analysis demonstrated that both suspensions had monomodal profiles and consequently, the nanoparticle populations were homogeneous. This analysis also corroborated the results of dynamic light scattering and laser diffraction, exhibiting a smaller mean diameter for the nanoparticles with copaiba oil and allantoin (143 nm) than for the nanoparticles with copaiba oil (204 nm). The physicochemical properties indicated that the dispersions were stable overtime. Rheology evidenced Newtonian behaviour for both suspensions. Antifungal susceptibility showed a MIC90 of 125 µg/mL (nanoparticles with copaiba oil) and 7.8 µg/mL (nanoparticles with copaiba oil and allantoin) against C. parapsilosis. The nanoparticles with copaiba oil and the nanoparticles with copaiba oil and allantoin presented a MIC90 of 500 µg/mL and 250 µg/mL, respectively, against C. krusei. The MIC90 values were 500 µg/mL (nanoparticles with copaiba oil) and 1.95 µg/mL (nanoparticles with copaiba oil and allantoin) against T. rubrum. Against M. canis, the nanoparticles with copaiba oil and allantoin had a MIC9 of 1.95 µg/mL. In conclusion, nanoencapsulation improved the antifungal activity of copaiba oil, which was enhanced by the presence of allantoin. The MICs obtained are comparable to those of commercial products and can represent promising therapeutics for cutaneous infections caused by yeasts and dermatophytes.


Subject(s)
Allantoin/chemistry , Allantoin/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Drug Compounding/methods , Fabaceae/chemistry , Lipids/chemistry , Nanoparticles/chemistry , Plant Oils/chemistry , Plant Oils/pharmacology , Allantoin/administration & dosage , Antifungal Agents/administration & dosage , Chemistry, Pharmaceutical , Fungi/drug effects , Microbial Sensitivity Tests , Particle Size , Plant Oils/administration & dosage , Rheology
16.
Acta Physiol (Oxf) ; 213(1): 19-38, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25204811

ABSTRACT

Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. Yet, in vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Many of the established approaches are invasive, hence not applicable in humans. Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) offers an alternative. BOLD-MRI is non-invasive and indicative of renal tissue oxygenation. Nonetheless, recent (pre-) clinical studies revived the question as to how bold renal BOLD-MRI really is. This review aimed to deliver some answers. It is designed to inspire the renal physiology, nephrology and imaging communities to foster explorations into the assessment of renal oxygenation and haemodynamics by exploiting the powers of MRI. For this purpose, the specifics of renal oxygenation and perfusion are outlined. The fundamentals of BOLD-MRI are summarized. The link between tissue oxygenation and the oxygenation-sensitive MR biomarker T2∗ is outlined. The merits and limitations of renal BOLD-MRI in animal and human studies are surveyed together with their clinical implications. Explorations into detailing the relation between renal T2∗ and renal tissue partial pressure of oxygen (pO2 ) are discussed with a focus on factors confounding the T2∗ vs. tissue pO2 relation. Multi-modality in vivo approaches suitable for detailing the role of the confounding factors that govern T2∗ are considered. A schematic approach describing the link between renal perfusion, oxygenation, tissue compartments and renal T2∗ is proposed. Future directions of MRI assessment of renal oxygenation and perfusion are explored.


Subject(s)
Diagnostic Imaging , Kidney Diseases/diagnosis , Kidney/pathology , Oxygen Consumption/physiology , Animals , Diagnostic Imaging/methods , Humans , Kidney Diseases/pathology , Kidney Function Tests/methods , Magnetic Resonance Imaging/methods
17.
Klin Monbl Augenheilkd ; 231(12): 1187-95, 2014 Dec.
Article in German | MEDLINE | ID: mdl-25519506

ABSTRACT

This review documents technical progress in ophthalmic magnetic resonance imaging (MRI) at ultrahigh fields (UHF, B(0) ≥ 7.0 T). The review surveys frontier applications of UHF-MRI tailored for high spatial resolution in vivo imaging of the eye, orbit and optic nerve. Early examples of clinical ophthalmic UHF-MRI including the assessment of melanoma of the choroid membrane and the characterisation of intraocular masses are demonstrated. A concluding section ventures a glance beyond the horizon and explores research promises along with future directions of ophthalmic UHF-MRI.


Subject(s)
Eye Neoplasms/pathology , Image Enhancement/methods , Magnetic Resonance Imaging/methods , Ophthalmoscopy/methods , Humans , Reproducibility of Results , Sensitivity and Specificity , Technology Assessment, Biomedical
18.
Photochem Photobiol Sci ; 13(9): 1253-60, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24977261

ABSTRACT

The oxidizing capacity and skin penetration of a commercial nanosized ZnO, Nanosun™ (Micronisers-Australia), were evaluated in vitro using porcine skin. Nanosun™ was initially characterized regarding its photo-reactivity and size distribution. An assay using methylene blue was performed to confirm the Nanosun™ photo-reactivity by exposing the labile molecule to UVA irradiation in the presence and absence of the nanosized ZnO. The nanosized ZnO was photo-reactive, reducing the methylene blue concentration to 7% while its concentration remained constant in the control formulation (without ZnO). The product label states that the average particle size is 30 nm. X-ray diffraction, nitrogen sorption and UV-spectrophotometry confirmed the presence of nanometric particles of approximately 30 nm. On the other hand, laser diffractometry showed micrometric particles in the size distribution profile. These analyses indicated that the nanoparticles are arranged as agglomerates and aggregates of micrometric proportions ranging from 0.6 to 60 µm. The skin lipid peroxidation was determined by the formation of thiobarbituric acid reactive species (TBARS) and quantified by UV-spectrophotometry. When exposed to UVA radiation the nanosized ZnO applied porcine skin showed a lower production of TBARS (7.2 ± 1.5 nmol g(-1)) than the controls, the MCT applied porcine skin (18.4 ± 2.8 nmol g(-1)) and the blank porcine skin (14.0 ± 2.0 nmol g(-1)). The penetration of ZnO nanoparticles was studied by scanning electron microscopy and energy dispersive X-ray spectroscopy. The tested ZnO particles did not penetrate into viable layers of the intact porcine skin. The particles tend to accumulate on the skin folds and in these regions they may penetrate into the horny layer.


Subject(s)
Zinc Oxide/chemistry , Animals , Lipid Peroxidation/drug effects , Lipid Peroxidation/radiation effects , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Methylene Blue/chemistry , Microscopy, Electron, Transmission , Particle Size , Skin/drug effects , Skin/radiation effects , Spectrometry, X-Ray Emission , Swine , Ultraviolet Rays
19.
J Biomed Nanotechnol ; 10(8): 1599-609, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25016659

ABSTRACT

Tacrolimus is widely used in the prophylaxis of solid-organ transplant rejection. Several studies have reported that tacrolimus has variable and poor bioavailability after oral administration, apart from adverse effects such as gastrointestinal disorders, hyperglycemia, nephro- and neurotoxicity. The aim of this work was to encapsulate tacrolimus (TAC) in lipid-core nanocapsules (LNC) as an oral strategy to deliver the drug. To validate our hypothesis, the pharmacodynamic effect of TAC-LNC was determined after oral and intraperitoneal (i.p.) administrations to mice. TAC-LNC had z-average diameter of 210 nm (unimodal), and 99.5% of encapsulation efficiency. In vitro sustained release was determined for TAC-LNC fitting an anomalous transport mechanism (n = 0.8). TAC-LNC demonstrated higher immunosuppressive activity after oral and i.p. administrations, when compared to the drug solution. TAC-LNC administered at 6.0 mg kg(-1) day(-1) showed equivalent percent reduction in lymphocyte when both routes of administration were used. After oral administration, drug nanoencapsulation allows reducing the dose by at least 40%. Furthermore, the nanoencapsulation of TAC in lipid-core nanocapsules showed pharmacodynamic effect similar for the oral and the i.p. routes. In conclusion, the lipid-core nanocapsules were able to improve the TAC deliver across the oral absorption barrier.


Subject(s)
Immunosuppressive Agents/pharmacology , Lipids/pharmacology , Nanocapsules/chemistry , Tacrolimus/pharmacology , Administration, Oral , Animals , Body Weight/drug effects , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/pharmacokinetics , Infusions, Parenteral , Lipids/administration & dosage , Lipids/chemistry , Lymphocytes/cytology , Lymphocytes/drug effects , Male , Mice , Nanocapsules/administration & dosage , Tacrolimus/administration & dosage , Tacrolimus/chemistry , Tacrolimus/pharmacokinetics
20.
Euro Surveill ; 19(10)2014 Mar 13.
Article in English | MEDLINE | ID: mdl-24650867

ABSTRACT

In 2013, a novel influenza A virus of subtype H7N9 was transmitted from avian sources to humans in China, causing severe illness and substantial mortality. Rapid and sensitive diagnostic approaches are the basis of epidemiological studies and of utmost importance for the detection of infected humans and animals. We developed various quantitative reverse transcriptase PCR (RT-qPCR) assays for (i) the generic detection of the haemagglutinin (HA) gene of H7 viruses or the neuraminidase (NA) gene of N9 viruses, and (ii) the specific detection of HA and NA of the novel avian H7N9/2013 virus. The sensitivity of the newly developed assays was compared with previously published PCRs, and the specificity of all RT-qPCRs was examined using a panel of 42 different H7 and 16 different N9 isolates. Furthermore, we analysed the performance of the RT-qPCR assays with dilution series and diagnostic samples obtained from animal experiments. Our study provides a comprehensive set of RT-qPCR assays for the reliable detection of the novel avian H7N9 virus, with high sensitivity and improved and tailored specificity values compared with published assays. Finally, we also present data about the robustness of a duplex assay for the simultaneous detection of HA and NA of the avian influenza H7N9/2013 virus.


Subject(s)
Influenza A Virus, H7N9 Subtype/genetics , Influenza A Virus, H7N9 Subtype/isolation & purification , Influenza in Birds/diagnosis , Influenza, Human/diagnosis , Nucleic Acid Amplification Techniques/methods , Animals , Birds , China , DNA Primers/genetics , DNA Probes/genetics , Humans , Influenza in Birds/virology , Influenza, Human/virology , Neuraminidase , Sensitivity and Specificity , Species Specificity
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